title: A phase II study of lapatinib, a dual EGFR and HER-2 tyrosine kinase inhibitor, in patients with castration-resistant prostate cancer.
abstract: OBJECTIVE
  Epidermal growth factor receptor (EGFR) and HER-2 tyrosine kinases may be involved in activation of androgen receptor and progression of prostate cancer. They represent potential therapeutic targets in prostate cancer. Lapatinib is an oral inhibitor of EGFR and HER-2. The objective of this study is to assess the preliminary clinical efficacy of lapatinib in the therapy of castration-resistant prostate cancer.
  
  
  METHODS
  In this multicenter, open-label trial, patients with rising PSA on androgen deprivation therapy and not having received chemotherapy were eligible. They were treated with lapatinib at a dose of 1,500 mg once daily. The primary end point was a >50% confirmed PSA decline from baseline; safety, tolerability, and time to PSA progression were secondary outcomes.
  
  
  RESULTS
  Twenty-nine patients enrolled in the study had a median age of 73 years and a baseline PSA of 21.6 ng/ml. Seven patients had no radiologic evidence of metastatic disease, while the remaining patients had bone or measurable disease or both. Treatment was well tolerated with only grade 3 treatment-related toxicities being diarrhea (14%) and rash (3%). One of 21 evaluable patients had >50% reduction in PSA, while another patient had 47% reduction in PSA with an ongoing duration of response of 45+ months. The median time to PSA progression was 29 days.
  
  
  CONCLUSIONS
  Lapatinib showed single agent activity in a small subset of unselected patients with castration-resistant prostate cancer, as measured by PSA. Future trials should explore a trial design with time-to-event end points and predictive biomarkers and a combination with other agents.
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. ywhang@med.unc.edu
authors.forename: Young E
authors.initials: YE
authors.lastname: Whang
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Armstrong
authors.forename: W Kimryn
authors.initials: WK
authors.lastname: Rathmell
authors.forename: Paul A
authors.initials: PA
authors.lastname: Godley
authors.forename: William Y
authors.initials: WY
authors.lastname: Kim
authors.forename: Raj S
authors.initials: RS
authors.lastname: Pruthi
authors.forename: Eric M
authors.initials: EM
authors.lastname: Wallen
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Crane
authors.forename: Dominic T
authors.initials: DT
authors.lastname: Moore
authors.forename: Gayle
authors.initials: G
authors.lastname: Grigson
authors.forename: Karla
authors.initials: K
authors.lastname: Morris
authors.forename: Catharine P
authors.initials: CP
authors.lastname: Watkins
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: George
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D000368:Aged; D000369:Aged, 80 and over; D002369:Castration; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D005500:Follow-Up Studies; D006801:Humans; D000077341:Lapatinib; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011799:Quinazolines / Q000627:therapeutic use*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors*; D015996:Survival Rate
chemical_list: D066246:ErbB Receptors; D000077341:Lapatinib; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; C512478:EGFR protein, human; C508053:ERBB2 protein, human